# RP11-439C15.4 inhibits the malignant progression of hepatocellular carcinoma via binding to DHX9 and facilitating its degradation: RP11-439C15.4 inhibits HCC progression by downregulating DHX9

## TL;DR

A long noncoding RNA called RP11-439C15.4 suppresses liver cancer by reducing DHX9 levels, offering new insights into cancer progression and treatment.

## Contribution

RP11-439C15.4 is identified as a tumor suppressor that inhibits HCC by binding and degrading DHX9.

## Key findings

- RP11-439C15.4 is significantly downregulated in hepatocellular carcinoma and linked to poor prognosis.
- RP11-439C15.4 inhibits HCC cell proliferation, invasion, migration, and sorafenib resistance.
- RP11-439C15.4 promotes DHX9 ubiquitination and degradation, suppressing HCC progression.

## Abstract

Long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and progression of hepatocellular carcinoma (HCC), but the functions and molecular mechanisms of large lncRNAs remain unclear. In this study, HCC data from The Cancer Genome Atlas (TCGA) and 116 HCC cases from our clinical center are used to identify a novel lncRNA, RP11-439C15.4, which is significantly downregulated in HCC. This downregulation is associated with poor prognosis in HCC patients. A series of
in vitro and
in vivo experiments demonstrate that RP11-439C15.4 significantly inhibits the proliferation, invasion, migration and sorafenib resistance of HCC cells. Further mechanistic investigations reveal that RP11-439C15.4 interacts with DExH-Box Helicase 9 (DHX9) to increase its ubiquitination and accelerate the degradation of DHX9, ultimately suppressing HCC progression. Modulation of DHX9 significantly reverses the effects of RP11-439C15.4 in HCC. In conclusion, this study identifies RP11-439C15.4 as a tumor suppressor and elucidates the regulatory mechanism of the RP11-439C15.4/DHX9 axis in HCC, providing valuable insights into the mechanisms of HCC progression and potential therapeutic targets.